DIET EFFECT ON ENERGY METABOLISM

这项研究的总体目标是表征神经内分泌和 提高饮食能量效率的细胞因素 易患肥胖症的动物的滞留。遗传肥胖(ob/ob)小鼠 将在大多数拟议的研究中使用。这种动物有一种突变 在ob基因中导致产生截短的和可能的 脂肪组织中的非功能ob蛋白。野生型肥胖蛋白是 由脂肪组织分泌，调节食物摄入量和能量平衡。 有待检验的一个假设是ob/ob小鼠中ob基因的突变。 导致中枢神经系统的调节发生改变 神经肽Y和促肾上腺皮质激素释放激素系统，而这些 改变也取决于糖皮质激素的存在或选定 饮食因素包括饮食中的葡萄糖或脂肪。建议进行研究以 确定脑室内注射地塞米松和/或 野生型肥胖蛋白对喂饲不同饲料的去肾上腺肥胖小鼠的影响 对神经肽V和促肾上腺皮质激素释放激素分泌的影响 选定的下丘脑部位。在平行研究中，下丘脑阻滞来自于 去肾上腺的ob/ob小鼠将在体外用地塞米松进行治疗。 和/或肥胖蛋白。神经肽Y与促肾上腺皮质激素释放激素 分泌物将被测量。另一个需要检验的假设是， OB基因突变导致胰腺早期发育印记 导致胰岛素调节持续缺陷的胰岛 葡萄糖诱导的胰岛素分泌的远端分泌本身。胰腺 2周龄ob/ob和瘦小鼠的胰岛将被培养以鉴定 这一缺陷的代谢基础。来自新生儿的胰岛和+/+ 将对老鼠进行检查，看看在出生和出生之间是否表达了印记 2周龄ob/ob小鼠。这些数据应该会增加我们对 饮食和神经激素依赖的代谢因素相互作用 肥胖蛋白在调节身体脂肪方面的作用，并应有助于确定 改进预防和控制肥胖症的营养方法。

The overall goal of this research is to characterize neuroendocrine and cellular factors responsible for the enhanced efficiency of dietary energy retention in obesity-prone animals. The genetically obese (ob/ob) mouse will be used in most of the proposed studies. This animal has a mutation in the ob gene that leads to production of a truncated and presumably nonfunctional ob protein in adipose tissue. Wild-type ob protein is secreted from adipose tissue to regulate food intake and energy balance. One hypothesis to be tested is that mutation of the ob gene in ob/ob mice leads to altered regulation in the central nervous system of the neuropeptide Y and corticotropin releasing hormone systems, and that these alterations also depend on the presence of glucocorticoids or selected dietary factors including dietary glucose or fat. Studies are proposed to determine how intracerebroventricular injection of dexamethasone and/or wild-type ob protein into adrenalectomized ob/ob mice fed various diets affects neuropeptide V and corticotropin releasing hormone secretion in selected hypothalamic sites. In parallel studies hypothalamic blocks from adrenalectomized ob/ob mice will be treated in vitro with dexamethasone and/or ob protein. Neuropeptide Y and corticotropin releasing hormone secretion will be measured. Another hypothesis to be tested is that the ob gene mutation causes an early developmental imprint in pancreatic islets that leads to a persistent defect in regulation of insulin secretion distal to glucose-induced insulin secretion per se. Pancreatic islets from 2 wk old ob/ob and lean mice will be cultured to characterize the metabolic basis for this defect. Islets from neonatal ob/ob and +/+ mice will be examined to see if an imprint is expressed between birth and 2 wk of age in ob/ob mice. These data should increase our understanding of the diet and neurohormonal-dependent metabolic factors that interact with ob protein in regulation of body fatness, and should aid in defining improved nutritional approaches to the prevention and control of obesity.